Prostate cancer, which occupies the number one in the morbidity rate and mortality in Europe and the United States, also shows a rapid increase in the morbidity rate also in Japan due to the westernization of the eating habits. The early-stage cancer of prostate cancer can be completely cured by operative treatment and the like, and elderly citizens with prostate cancer or progressive cancer, for whom an operative treatment is difficult, undergo a hormone therapy. During such treatment, however, hormone therapy resistant prostate cancer emerges, and therefore, an effective treatment method of prostate cancer has not been currently established as the situation stands.
On the other hand, pancreatic cancer is held to be one of the cancers most difficult to treat at present. In pancreatic cancer, even when the tumor is removed by surgery, about 90% of them have a relapse and die. For topical progressive irremovable pancreatic cancer, multiple drug combination therapy mainly using gemcitabine hydrochloride and 5-FU and the like are applied, and when distant metastasis is found, a multiple drug combination therapy mainly using gemcitabine hydrochloride, and the like are applied. Nevertheless, the prognosis is 4-6 months in a median value.
Lung cancer is the top in the number of those died of cancer in Japan. Particularly, the number of patients of non-small cell lung cancer is the highest in the lung cancer. As a therapeutic drug therefor, chemotherapeutic agents such as taxane group and the like have been used; however, only about 30% regression is observed. As a molecular target drug, gefitinib is applicable to patients having mutated EGFR
Therefore, the development of an effective therapeutic drug for these types of cancer is desired, and the foundation for drug discovery needs to be established early.
A novel gene (Prostate Cancer Antigen-1: PCA-1) has been reported, which highly expresses in prostate cancer, and does not show high expression in normal prostate epithelial cell and benign prostatic hyperplasia which is a benign tumor (non-patent document 1, non-patent document 2). There have been reported a method using the expression state of PCA-1 for the diagnosis of prostate cancer (patent document 1), and an apoptosis promoter, a cell proliferation inhibitor, an agent for the prophylaxis or treatment of cancer and the like, which contain, as an active ingredient, a compound that suppresses the expression or function of PCA-1 (patent document 2). PCA-1 is also highly expressed in pancreatic cancer (patent document 3) and non-small cell lung cancer (non-patent document 3). When the PCA-1 expression in these cancer cells was suppressed using siRNA, a remarkable suppressive action on the growth of prostate cancer cell (patent document 2), pancreatic cancer cell (patent document 3), and non-small cell lung cancer was observed (non-patent document 3). In addition, a tumor formed by transplanting cancer cells to a mouse showed regression by the administration of siRNA to PCA-1. These results suggest that PCA-1 can be a new molecular target in the cancer treatment for prostate cancer, pancreatic cancer and the like.
Moreover, since tRNA demethylated by PCA-1 increases the protein translation efficiency, PCA-1 is also useful for the diseases (e.g., brain neurodegenerative disease, arteriosclerosis) possibly caused by an abnormal protein.
On the other hand, a benzimidazole derivative having the following structure has been reported (patent documents 4, 5); however, its action on the enzyme activity of PCA-1 is not known.
